Clinical Trials /

A Study to Test the Safety of Immunotherapy With Nivolumab Alone or With Ipilimumab Before Surgery for Bladder Cancer Patients Who Are Not Suitable for Chemotherapy

NCT03520491

Description:

The purpose of this study is to test if immunotherapy with nivolumab alone or in combination with ipilimumab is safe and does not delay the planned bladder cancer surgery. The investigators want to see if treatment with these drugs prior to surgery may decrease the size of the bladder cancer and thus could help make the surgery more successful.

Related Conditions:
  • Bladder Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Test the Safety of Immunotherapy With Nivolumab Alone or With Ipilimumab Before Surgery for Bladder Cancer Patients Who Are Not Suitable for Chemotherapy
  • Official Title: A Pilot Study to Evaluate the Safety of Neoadjuvant Nivolumab Alone or in Combination With Ipilimumab for Cisplatin-Ineligible Patients With Muscle Invasive Bladder Cancer (CA209-9DJ)

Clinical Trial IDs

  • ORG STUDY ID: 18-042
  • NCT ID: NCT03520491

Conditions

  • Bladder Cancer

Interventions

DrugSynonymsArms
NivolumabCohort 1
IpilimumabCohort 2

Purpose

The purpose of this study is to test if immunotherapy with nivolumab alone or in combination with ipilimumab is safe and does not delay the planned bladder cancer surgery. The investigators want to see if treatment with these drugs prior to surgery may decrease the size of the bladder cancer and thus could help make the surgery more successful.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalNivolumab 3 mg/kg on day 1 of each cycle for a total of 5 cycles. Each cycle will be two weeks long and treatment will occur during weeks 0, 2, 4, 6, and 8.
  • Nivolumab
Cohort 2ExperimentalIpilimumab 3 mg/kg and Nivolumab 1 mg/kg on day 1 of each cycle, followed by Nivolumab 3 mg/kg on day 22 of each cycle for a total of 2 cycles. Each cycle will be six weeks long. Ipilimumab and Nivolumab will occur on weeks 0 and 6 while Nivolumab alone will occur on weeks 3 and 9.
  • Nivolumab
  • Ipilimumab
Cohort 3ExperimentalIpilimumab 3 mg/kg on day 1 each cycle and Nivolumab 1 mg/kg on day 1 of each cycle for a total of 3 cycles. Each cycle will be three weeks long and treatment will occur during weeks 0, 3, and 6.
  • Nivolumab
  • Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of urothelial carcinoma of the bladder. Variant
             histology is acceptable if there is a predominant urothelial component.

          -  Cystoscopically and radiographically confirmed cT2-4a cN0 cM0 disease. Patients with
             cT4a disease invading into the prostatic stroma with no cystoscopic confirmation of
             muscle invasion are eligible.

          -  Patients ineligible for cisplatin based on any of the following criteria:

               -  Estimated or calculated creatinine clearance ≥ 30ml/min but < 60 ml/min

               -  Grade 2 or above audiometric hearing loss (per CTCAE v4.0)

               -  Grade 2 or above peripheral neuropathy (per CTCAE v4.0)

          -  Availability of tumor specimen block or 30 unstained slides from diagnosis of
             muscle-invasive disease. Patients with fewer than 30 slides available may be enrolled
             after discussion with the Principal Investigator.

          -  Karnofsky performance status ≥ 70%.

          -  Age ≥ 18 years.

          -  Required initial laboratory values:

               -  Absolute neutrophil count ≥ 1.5 x 10^9/L

               -  Platelets ≥ 100 x 10^9/L

               -  Bilirubin ≤1.5 times the upper limit of normal (x ULN)

               -  Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN

               -  PTT/PT ≤1.5 x ULN or INR < 1.7 x ULN for patients who are not receiving
                  therapeutic anticoagulation. Patients receiving therapeutic anticoagulation
                  should be on a stable dose.

        Exclusion Criteria:

          -  Prior treatment with systemic chemotherapy for bladder cancer. (Prior intravesical
             treatment is allowed.)

          -  Prior bladder-directed radiotherapy.

          -  Presence of active autoimmune disease, symptoms, or conditions, with the following
             exceptions:

             °Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to
             autoimmune thyroiditis only requiring hormone replacement, asymptomatic laboratory
             evidence of autoimmune disease (e.g.: +ANA, +RF, anti-thyroglobulin antibodies), or
             conditions not expected to recur in the absence of an external trigger are permitted
             to enroll.

          -  Subjects with a condition requiring systemic treatment with either corticosteroids
             (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14
             days of first dose of study drug. Inhaled or topical steroids, and adrenal replacement
             steroid doses are permitted in the absence of active autoimmune disease.

          -  Unstable angina.

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure.

          -  History of myocardial infarction within 6 months.

          -  History of stroke within 6 months.

          -  Evidence of bleeding diathesis or coagulopathy. Therapeutic anticoagulation is
             permitted, but patients must be on a stable dose.

          -  Major surgical procedure within 28 days prior to the study.

          -  Serious, non-healing wound, ulcer, or bone fracture.

          -  Other prior malignancy active within the previous 2 years except for local or
             organ-confined early stage cancer that has been definitively treated with curative
             intent or does not require treatment, does not require ongoing treatment, has no
             evidence of active disease, and has a negligible risk of recurrence and is therefore
             unlikely to interfere with the endpoints of the study.

          -  Subjects who have received prior therapy with any T cell co-stimulation or checkpoint
             pathways such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-CD137; or other
             medicines specifically targeting T cells are prohibited. Prior IL-2 is permitted.

          -  Prior therapy with intravesical BCG within 6 weeks of treatment.

          -  Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBV sAg) test or
             positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV
             antibody test indicating acute or chronic infection.

          -  Known history of testing positive for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (AIDS).

          -  History of allergy to study drug component or history of severe hypersensitivity
             reaction to any monoclonal antibody.

          -  Women who are breastfeeding or pregnant as evidenced by a positive pregnancy test
             within 14 days of first dose.

          -  Male subjects who are unwilling to use contraception during the treatment and for at
             least 31 weeks after the last dose of study treatment (5 half-lives of study drug plus
             90 days duration of sperm turnover).

          -  Women of childbearing potential (WOCBP) not using a medically acceptable means of
             contraception throughout the study treatment and for at least 23 weeks following the
             last dose of study treatment (5 half-lives of study drug plus 30 days duration of
             ovulatory cycle).

               -  WOCBP are defined as those who have experienced menarche and who have not
                  undergone successful surgical sterilization (hysterectomy, bilateral tubal
                  ligation, or bilateral oophorectomy) or are not postmenopausal. Post-menopausal
                  is defined as:

               -  Amenorrhea ≥ 12 consecutive months without another cause, or

               -  For women with irregular menstrual periods and on hormone replacement therapy
                  (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL

          -  Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (e.g., infectious disease) illness.

          -  Inability to comply with study and/or follow-up procedures.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:number of patients who proceed to radical cystectomy and pelvic lymph node dissection
Time Frame:within 60 days after completion of neoadjuvant nivolumab or nivolumab in combination with ipilimumab
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Immunotherapy
  • Nivolumab
  • Ipilimumab
  • 18-042

Last Updated